tbuckley/cabot-search huggingface dataset:
P01.09.A Prevalence and predictors of cognitive impairment in adult glioma survivors after multimodal therapy
Authors: L De Roeck, P Spiessens, H Vermeulen, P Clement, J Daisne, S De Vleeschouwer, C Sleurs, M Lambrecht
Journal: Neuro-Oncology (2022)

Abstract Background Long-term survival can be achieved in an increasing number of glioma patients after treatment. Therefore, safeguarding these survivors’ quality of life (QoL) is essential. Neurocognitive decline arises in many young patients, placing a heavy burden on the social and economic aspects of the patients’ lives. A lot of debate is currently ongoing regarding the prevalence of neurocognitive impairment and individual predictors of whom is susceptible for such side effect. Material and Methods In this cross-sectional study, 37 WHO grade 2-3 adult glioma survivors, at least one year after multimodal therapy, were tested using a comprehensive neurocognitive test battery covering multiple cognitive domains. Neurocognitive test scores were converted into z-scores using country-specific normative data. Cognitive impairment was defined as a z-score lower or equal to -1.50 for each subtest. Age, time since multimodal therapy, radiotherapy treatment and tumour location were included as predictors in a linear regression model per outcome (n=12). Results In this cohort, 29 patients (78%) showed a test score below the predefined cutoff on at least one cognitive test. The percentage of patients who showed test-specific cognitive impairment ranged from 8.1% to 56.76% per test. Fine motor skills, verbal memory, processing speed and executive functioning were the most commonly affected cognitive domains. In this study, the variability in processing speed performance was associated with age (TMT A, p=0.03), time since therapy (WAIS-IV coding, p=0.02) and tumour location. In these measures, poorer outcomes were observed with increasing age, longer time since therapy and in patients with gliomas located in the left frontal lobe. Moreover, age showed to be a significant predictor of verbal memory, with poorer outcomes on the HVLT-R delayed recall task with increasing age (p=0.04). Tumour location predicted working memory performance, as patients with right parietal tumours (p=0.03) showed significantly worse on the WAIS-IV digit span task. Conclusion These preliminary data underline the various alterations of neurocognitive functioning in glioma survivors after multimodal therapy. Therefore, future research needs to shift towards a patient-tailored approach. The next step in this study will be to link these neurocognitive data to advanced neuroimaging data to explore the potential predictive value of imaging markers for neural damage and cognitive outcomes, paving the path to innovative treatment planning techniques.
P11.10.A An assessment of predictive factors for overall survival in glioblastoma - MGMT methylation is solely important for younger patients
Authors: A Krigers, T Cosar, J Kerschbaumer, M Demetz, D Pinggera, C Thomé, C F Freyschlag
Journal: Neuro-Oncology (2022)

Abstract Background Diverse groups of factors - neuropathological characters, tumor position and epidemiological data - have been proposed for outcome evaluation of glioblastoma (GBM). We compared clinical signs, neuropathological features and the locus of the tumor with the follow-up data. Material and Methods All adult patients with firstly diagnosed and histologically proven GBM (according to WHO 2016), which were operated in our center between January 2010 and June 2021 were retrospectively assessed. Epidemiological, clinical and neuro-pathological characteristics were acquired from our institutional neuro-oncological database. Results A total of 399 patients could be evaluated. The mean follow-up was 13.9 months (CI95 12.2-15.6), within 266 (67%) patients were deceased. Estimated mean OS for entire cohort was 24.2 months (CI95 19.8-28.7). Age, MGMT promoter methylation, brainstem localization or if a patient received biopsy only showed significant impact on OS. Each year of life accounted for 3.4% additional hazard to decease (HR=1.034, CI95 1.020-1.048, p&amp;lt;0.001). If patients were younger than 65 years, mean OS was 34 months (CI95 26.5-41.8) compared to older than 65 years patients with a mean OS of 14.3 months (CI95 10.5-18.1, p&amp;lt;0.001). Generally, an unmethylated MGMT promoter status was linked to 75% higher hazards to decease (HR 1.75, CI95 1.27-2.40, p=0.027). If MGMT promoter status was methylated, mean OS was 25.7 months (CI95 19.9-31.5) or more compared to unmethylated with 14.5 months (CI95 12.0-16.9, p=0.01). Presence of MGMT promoter methylation showed influence on OS only in the younger cohort (&amp;lt;65y, mean OS 38.7 months [CI95 28.9-48.6]; HR 2.60 [CI95 1.55-4.37], p&amp;lt;0.001) as opposed to unmethylated MGMT (mean OS 17.7 months [CI95 14.1-21.2], p&amp;lt;0.001). In the older cohort (&amp;gt;65y) presence of methylated MGMT promoter showed no significant difference (p=0.364). For patients who received only biopsy, 2.4 times more hazards for worse OS were revealed (HR 3.36, CI95% 2.30-4.90, p&amp;lt;0.001). In these cases, mean OS was 7.1 months (CI95 5.3-8.8). Other factors, including gender or preoperative seizures, as well as EGFR, p53, IDH1, ATRX and TERT status did not show impact on OS in our series. Conclusion In our cohort, MGMT promoter methylation showed an impact on OS only in younger patients &amp;lt;65 years of age. Biopsy of GBM should only be considered very selected patients when resection is not possible.
P16.02.B Leptomeningeal dissemination in gliomas in National Research Institute of Oncology in Gliwice experience
Authors: E Nowicka, H Grzbiela, K Widera, L Zarudzki, A Grządziel, R Tarnawski
Journal: Neuro-Oncology (2022)

Abstract Background The leptomeningeal dissemination (LMD) in the course of gliomas is rare. According to literature it can affect 4.7% of all patients with gliomas. LMD can be diagnosed at the initial presentation or at the time of recurrence. The standard therapy has not yet been determined. We aimed to present the clinical features and prognosis in retrospective analysis of patients with LMD in gliomas in National Institute of Oncology in Gliwice, Poland experience. Material and Methods Twenty patients with leptomeningeal dissemination in course of treatment of brain gliomas were identified. There were 16 men and 4 women. Median age of pts was 35,5 y (range 18-51). All tumours were supratentorial at diagnosis. There were 6 Diffuse Astocytomas, 3 oligodendrioglimas and 11 glioblatomas. In two patients LMD was found at initial diagnosis of GBM. The majority of patients (15 pts) presented clinical symptoms and in 5 asymptomatic pts LMD was diagnosed in MRI. The diagnosis was confirmed in craniospinal MRI. One patient was operated due to rapid clinical progression of spinal compression symptoms. All but one patient were offered palliative therapy. Radiotherapy was prescribed to 16 patients: in 7 pts for whole brain to C2, in 3 pts for craniospinal axis, in 7 for spinal canal and in 2 pts local therapy was performed. Mean dose of RT was 28,7 Gy/g (range 18-45 Gy/g). In 8 patients radiotherapy was combined with chemotherapy and chemotherapy as sole treatment was prescribed to 2 pts (Lomustin, EP). Results Mean time from initial diagnosis to LMD diagnosis was 46 mo (range 0,4-199 mo) for all patients and for non-GBM and GBM patients were 81,4 mo (16-199 mo) and 14,0 mo (0,4-27 mo) respectively. In 7 patients LMD was diagnosed concurrently with local relapse. In remaining mean time from local relapse to LMD was 4,6 mo (1,2-20,0 mo). Mean OS dated from time of LMD diagnosis for whole group was 5,9 mo (0,4-27 ), for non-GBM and GBM patients were 9,2 mo (3,6-27 mo) and 2,94 (0,4-12,7 mo) respectively. The palliative effect as improvement in clinical symptoms was achieved in 15 pts. Conclusion LMD in gliomas is rare but should be kept in mind while clinical symptoms in glioma patients occur. The prognosis of LMD is poor. Radiotherapy have palliative intent and it can affect the clinical symptoms and survival.
P15.12.A Amine CEST contrast in gliomas to measure metabolic treatment effect at 7T
Authors: B Abecassis Schmitz, E Ercan, J de Bresser, L Dirven, M J B Taphoorn, M J P van Osch, J A F Koekkoek
Journal: Neuro-Oncology (2022)

Abstract Background Chemical exchange saturation transfer (CEST) is an imaging technique that generates contrast based on proton exchange between water and a solute pool of interest. CEST is sensitive to molecules containing amine groups such as glutamate and creatine. Since creatine is a crucial metabolite in cellular metabolism and deregulation in cellular bioenergetics is a hallmark of cancer, CEST could be relevant for glioma imaging, specifically when evaluating treatment response. No clear consensus has been established on its use, therefore we wanted to preliminarily investigate the presence of amine CEST contrast in the contrast enhanced (CE) and non-enhanced (NE) lesions of gliomas, and to assess whether treated tumors would display different CEST contrast compared to treatment naïve tumors. Material and Methods We prospectively scanned 12 glioma patients on a whole-body 7 Tesla Philips Achieva MRI scanner (7 treated glioblastomas; 4 treatment naïve glioblastomas; 1 treatment naïve low-grade astrocytoma). Treatment included surgical resection, chemotherapy and radiotherapy. All patients gave informed consent. CEST images were post-processed, including corrections for B0 and B1 inhomogeneities. The CEST Z-spectra and magnetization transfer ratio (MTR) asymmetry were calculated per voxel. To retrieve the CEST values within the tumor lesions and contralateral white matter for normalization, segmentations were manually delineated on the clinical T2-FLAIR or post contrast 3D-T1. Results Overall we observed a relative increase of amine CEST contrast in the CE (MTRasym: Mean (x̄)=1.32; Standard deviation (σ)= 0.28) compared to a relative decrease (MTRasym: x̄=1.20; σ= 0.35) in the NE lesion. When evaluating the results from the CE and NE lesions for treated and treatment naïve groups individually, we observed a slightly different trend. In the treatment group, the CE lesions showed a higher amine CEST contrast (MTRasym: x̄=1.38; σ= 0.30) than the NE (MTRasym: x̄ = 1.11; σ = 0.302). In contrast, in the treatment naïve group, the CE lesion showed a slightly lower CEST contrast (MTRasym: x̄ = 1.23; σ=0.21) than in the NE group (MTRasym: x̄ = 1.29; σ= 0.38). Conclusion Our results show different amine CEST contrast trends between treated and treatment naïve groups when comparing CE and NE lesions. This suggests that treatment may have an effect on tumor tissue bioenergetics affecting the concentration of creatine. Nevertheless, future work is necessary to verify our results in a larger group of patients.
P11.34.A Pseudoprogression in cases of brain metastases and its neurooncological pitfalls under PD-1 inhibitor therapy in the era of personalized medicine
Authors: T Schulz, A Cattaneo, M Löhr, V Dufner, C Monoranu, A Keßler
Journal: Neuro-Oncology (2022)

Abstract Background Immunotherapy plays an increasing role in combating malignant cancers. Recently, there has been a noticeable uptick of pseudoprogression mimicking true tumor growth or even intracranial abscess. PD-1 inhibitors especially have come under scrutiny for imitating progressive diseases. Here, we summarize our departmental findings to this regard. Material and Methods We analyzed the clinical, intraoperative and neuropathological findings as well as perioperative radiological imaging in four cases. Results Four patients (three males and one female, ranged 52-74 years) underwent resection for brain metastases and were subsequently treated with radiotherapy and with PD-1 inhibitors. Within one-year post-surgery, cranial MRI-imaging showed space-occupying, contrast enhanced lesions in all four patients. In two cases FET-PETs were performed pre-operatively. They showed a significant increase in aminoacid uptake. In two cases, 5-aminolevulineacid (5-ALA) was applied pre-operatively. In one case, there was considerable 5-ALA uptake. The fourth patient presented radiological signs of an abscess and underwent emergency surgery. The neuropathological workup of all tissues in question depicted highly increased activity of lymphocytes and microglia, accompanied by necrosis. All cases were classified as pseudoprogression, which, on top, had developed supramarginally in previously healthy tissue. Conclusion Neurooncologists face crescent challenges in the increasing cases of pseudoprogression under/after immunotherapy. Radiological imaging doesn’t seem to be able to clearly differentiate between true and pseudoprogression. Even FET-PETs, in general a valid diagnostic tool, seem to be fooled by checkpoint inhibitors. Furthermore, pseudoprogressive tissue after PD-1 inhibitor therapy might mimic tumor tissue intra-operatively by increased 5-ALA uptake. All these characteristics increase the risk of overly aggressive resection of the suspected cancerous or infectious, but in the end pseudo-progressive tissue. Brain edema and clinical symptoms spurred by pseudoprogression may be an indication for surgery, but the risk of performing possibly unnecessary surgery based on radiological findings fooled by PD-1 inhibitors should be taken into consideration. At this point, there does not seem to be a foolproof diagnostic method to differentiate pseudo- from true progression. And there is the possibility that the pseudoprogression is happening in tissue adjacent to the previously resected lesion. Neurooncologists need to acknowledge that pseudoprogression under/after immunotherapy will become only more prevalent in the future and take this message to their patients.
P15.03.A The value of 7 Tesla MR spectroscopic imaging for improved preoperative determination of the tumor grade and IDH status in gliomas: preliminary data
Authors: G Hangel, S Sharma, C Cadrien, J Furtner, J Furtner, T Roetzer-Pejrimovsky, M Preusser, W Bogner, K Rössler, S Trattnig, G Widhalm
Journal: Neuro-Oncology (2022)

Abstract Introduction A new generation of MR spectroscopic imaging (MRSI) methods using 7T scanners have demonstrated the capability to resolve more neuro- and oncometabolites at higher resolutions than clinical routine MRSI. In a cohort of glioma patients, we explored the automated preoperative and noninvasive classification of IDH-mutation status and tumor grade based on 7T MRSI. Methods This retrospective study included 36 patients (15 female) with histologically confirmed diffusely infiltrating glioma WHO grade 2-4 (9 grade 2, 9 grade 3 and 18 grade 4) and known IDH status (21 IDH1-mut, 15 IDH-wt) with an available 7T MRSI scan of sufficient data quality. The 3D MRSI scan had a 3.4 mm isotropic resolution and 15 minutes acquisition time. 12 spectral components were classified voxel-wise, including choline, glutamine and glycine. Within a tumor segmentation based on routine 3T imaging, we used a random forest algorithm for the voxel-wise classification of IDH mutation and grade (into low or high grade). Training used the leave-one-out cross validation method (i.e., for every patient data set, the other 35 datasets were used as training set) and feature selection out of the available combinations for metabolite ratios (e.g., glutamine to choline). The resulting voxel classifications were aggregated into a mean probability per patient that was the base for receiver-operator characteristic (ROC) curves both for grade and IDH status. Results The classification algorithm obtained an area under the curve (AUC) for IDH determination of 0.85 (e.g., 75% sensitivity and 95% specificity). For grade determination, the AUC was 0.88 (e.g., 87% sensitivity and 89% specificity). In comparison, the AUC per voxel would have resulted in an AUC of 0.66 for both. Further, classification by individual metabolite ratios resulted in lower AUCs in all cases. Conclusions According to our preliminary data, preoperative 7T MRSI is capable to determine the correct glioma grade and IDH status with high sensitivity and specificity by leveraging the extended metabolic panel width and voxel amount. By increasing this cohort in future, we intend to confirm our initial results and we also plan to extend classification to more molecular-pathological features (e.g., TERT). Thus, even a voxel-wise classification of tumor microenvironments could be attempted. Further improvements in 7T MRSI methodology such as absolute instead of relative quantification would also aid these attempts. In summary, 7T MRSI has shown its potential for improved preoperative characterization of gliomas.
P11.20.A Correlation between thyroid function and regorafenib activity in recurrent IDH wild-type(IDHwt) glioblastoma(GBM) patients: a large monocentric study
Authors: M Caccese, M Padovan, G Cerretti, F Cavallin, V Zagonel, G Lombardi
Journal: Neuro-Oncology (2022)

Abstract Background Glioblastoma is the most frequent CNS malignant tumor, with high aggressiveness and poor prognosis. Regorafenib has recently demonstrated promising activity in terms of survival in recurrent glioblastoma patients. The impact of thyroid function on regorafenib activity has alreasy described in in patients with other types of tumors. This study aimed to investigate the relationship between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4 ratio) and survival in IDHwt GBM patients who were treated with regorafenib. Material and Methods We retrospectively evaluated all consecutive recurrent IDHwt GBM patients who were treated with regorafenib at the Veneto Institute of Oncology in Padua (Italy) for which baseline thyroid function assessment was available prior to starting regorafenib. Major inclusion criteria were: histological diagnosis of IDHwt glioblastoma, regorafenib as second-line treatment, basel thyroid values available.The relationships between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4 ratio) and outcomes (PFS, OS) were investigated with Cox regression models, where thyroid variables were modeled with first order polynomial or restricted cubic splines. Results We enrolled 108 recurrent IDHwt glioblastoma patients treated with regorafenib at our center From November 2015 to January 2022: 70% were male and median age was 50 years old. All patients received post-surgical treatment with concomitant chemotherapy and subsequent temozolomide according to Stupp protocol as first-line therapy. 32 patients (30%) underwent a second surgery upon recurrence. From starting regorafenib the median follow-up was 7.3 months (IQR 4.0-12.7). MedianPFS was 2.2 months (95% CI 2.0 to 3.4), and PFS rate was 43-13-4% at 3-6-12ms, respectively. MedianOS was 10.4 months (95% CI 7.5 to 14.5), and OS rate was 92-70-46% at 3-6-12 months, respectively. Disease Control Rate (DCR) was 42.7%. Univariate analysis suggested that the relationship between PFS and baseline fT4 may be modelled with first order polynomial (linear term p=0.06, non-linear term p=0.61) and also suggested a non-linear relationship between PFS and baseline fT3/fT4 (linear term p=0.06, non-linear term p=0.04).When adjusting for major clinical confounding factors (age, ECOG PS, second surgery, MGMT), multivariate analysis identified that baseline fT4 (as a continuous variable) is an independent risk factor for PFS (HR 1.09, 95% CI 1.02 to 1.17; p=0.02). We did not find any statistically significant associations between all baseline thyroid variables with OS and response. Conclusion Our study demonstrated fT4 value to be a predictive biomarker of PFS in recurrent glioblastoma patients treated with regorafenib. No correlation was showed between baseline thyroid function and survival.
P09.03.A Associations of levetiracetam use with the safety and tolerability of chemoradiotherapy for patients with newly diagnosed glioblastoma
Authors: K Seystahl, F B Oppong, E Le Rhun, C Hertler, R Stupp, B Nabors, O Chinot, M Preusser, T Gorlia, M Weller
Journal: Neuro-Oncology (2022)

Abstract Background Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap. Patients and Methods In a retrospective analysis of individual patient data using a pooled cohort of patients with newly diagnosed glioblastoma included in clinical trials prior to chemoradiotherapy (CENTRIC, CORE, AVAglio) or prior to maintenance therapy (ACT-IV), we tested associations of hematologic toxicity, nausea or emesis, fatigue, and psychiatric adverse events during concomitant and maintenance treatment with the use of LEV alone or with other AED versus other AED alone or in combination versus no AED use at the start of chemoradiotherapy and of maintenance treatment. Results Of 1681 and 2020 patients who started concomitant chemoradiotherapy and maintenance temozolomide, respectively, 473 and 714 patients (28.1% and 35.3%) were treated with a LEV-containing regimen, 538 and 475 patients (32.0% and 23.5%) with other AED, and 670 and 831 patients (39.9% and 41.1%) had no AED. LEV was associated with higher risk of psychiatric adverse events during concomitant treatment in univariable and multivariable analyses (RR 1.86 and 1.88, p&amp;lt;0.001) while there were no associations with hematologic toxicity, nausea or emesis, or fatigue. LEV was associated with reduced risk of nausea or emesis during maintenance treatment in multivariable analysis (HR=0.80, p=0.017) while there were no associations with hematologic toxicity, fatigue, or psychiatric adverse events. Conclusion Any association of psychiatric adverse events with LEV did not persist beyond the concomitant treatment phase. Antiemetic properties of LEV may be beneficial during the maintenance temozolomide.